title: Occupational exposure to hepatitis C virus: early T-cell responses in the absence of seroconversion in a longitudinal cohort study.
abstract: BACKGROUND
  T-cell responses have been described in seronegative patients who test negative for hepatitis C virus (HCV) RNA despite frequent HCV exposure. However, the cross-sectional design of those studies did not clarify whether T cells were indeed induced by low-level HCV exposure without seroconversion or whether they resulted from regular acute infection with subsequent antibody loss.
  
  
  METHODS
  Over a 10-year period, our longitudinal study recruited 72 healthcare workers with documented HCV exposure. We studied viremia and antibody and T-cell responses longitudinally for 6 months.
  
  
  RESULTS
  All healthcare workers remained negative for HCV RNA and antibodies. However, 48% developed proliferative T-cell response and 42% developed responses in interferon-gamma enzyme-linked immunosorbent spot assays, with 29 healthy HCV-unexposed controls used to define assay cutoffs. The response prevalence was associated with the transmission risk score. T-cell responses peaked at week 4 and returned to baseline by week 12 after exposure. They predominantly targeted nonstructural HCV proteins, which are not part of the HCV particle and thus must have been synthesized in infected cells.
  
  
  CONCLUSIONS
  Subclinical transmission of HCV occurs frequently, resulting in infection and synthesis of nonstructural proteins despite undetectable systemic viremia. T-cell responses are more sensitive indicators of this low-level HCV exposure than antibodies.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
authors.forename: Theo
authors.initials: T
authors.lastname: Heller
authors.forename: Jens Martin
authors.initials: JM
authors.lastname: Werner
authors.forename: Fareed
authors.initials: F
authors.lastname: Rahman
authors.forename: Eishiro
authors.initials: E
authors.lastname: Mizukoshi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sobao
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Gordon
authors.forename: Arlene
authors.initials: A
authors.lastname: Sheets
authors.forename: Averell H
authors.initials: AH
authors.lastname: Sherker
authors.forename: Ellen
authors.initials: E
authors.lastname: Kessler
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Bean
authors.forename: Steven K
authors.initials: SK
authors.lastname: Herrine
authors.forename: M'lou
authors.initials: M
authors.lastname: Stevens
authors.forename: James
authors.initials: J
authors.lastname: Schmitt
authors.forename: Barbara
authors.initials: B
authors.lastname: Rehermann
mesh_terms: D000917:Antibody Formation; D049109:Cell Proliferation; D005260:Female; D006282:Health Personnel; D016174:Hepacivirus; D006526:Hepatitis C / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood; D018936:Hepatitis C Antigens / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D016273:Occupational Exposure; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology*; D014766:Viremia / Q000276:immunology*
chemical_list: D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D012367:RNA, Viral; D007371:Interferon-gamma
keywords: T cell; antibody; exposure; healthcare worker; hepatitis; needlestick